Uranium and The Creatures Who Breathe It
There’s an old comic from XKCD about the “purity” of the different fields of scientific study.
While great advances in one scientific field may seem to occur in a corner, there is a vertical integration across disciplines inherent in the consistency of their physical principles. If biologists and chemists meant a fundamentally different thing when they said “carbon-carbon bond” or “one degree Celsius,” the system by which “science” generally classifies and investigates the physical world would be uselessly idiosyncratic. Rather, each discipline has either large pictures or the small details to fill in missing pixels, and all these pictures are part of the same landscape — the observable universe.
Biochemistry is where biology’s coherent framework is populated by the details of chemistry, and a basic understanding of both systems of knowledge enables the whole. That enmeshment is why anyone who has taken a biochemistry course (probably) had to take biology and chemistry first, and why we should be loathe to forget what we learn from either field. When coloring the complete picture of “science,” field purity may be its own sin.
Purity in the form of a coherent abstraction comes easily under duress of a biochemistry exam, when each reaction is a magical, memorized process. One thing reacts with another, there’s an enzyme involved, voila, you’ve earned an A! This omission of molecular dynamics and thermochemical details serves us well as a shorthand, and such layers of abstraction are a necessary evil for looking at complicated biochemical systems.
We’re concerned here with the very small pictures that enable those abstractions. Dipping our feet into chemistry for a few minutes can bring us a little closer to knowing why cells do what they do…and the unexpected ways they might be able to do it.
Life is Electric
Life is sustained by electrons being transferred from one molecule (an electron donor) to another (an electron acceptor). This transfer releases energy as both molecules transform to more stable products. Humans are familiar with the overall reaction of sugars (like glucose) to water and carbon dioxide.
In our case, the carbon atoms in sugar molecules are the electron donor. The electron acceptor is the oxygen we breathe. As the original carbon bonds in the sugar are broken, the electrons near each carbon atom are bonded to oxygen molecules. The energy released as your body disassembles the sugar is transformed to heat (keeping your body a toasty ~98 degrees Fahrenheit) and into bonds in compounds like adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH/NAD+), which provide on-demand chemical energy to all other cellular reactions.
Sugar does not entirely vanish into carbon dioxide. Our metabolism converts sugars and other nutrients into a wide variety of compounds. Metabolism at the cellular level must accomplish two goals: convert raw materials into chemical energy (catabolism) and synthesize cellular building blocks such as proteins, lipids, and DNA (anabolism). Our cells have the fortune of using carbon-based fuels that can provide both energy and building blocks.
The Battery in the Cell
The energy released during electron transfer has a “potential,” just like the voltage of a battery. In fact, each donor/acceptor pair react like the anode and cathode of a battery, and potential is a measure of how spontaneous the flow of energy is. If the potential is high, the electricity flows: the paired reaction proceeds, and the cell keeps chugging happily.
The redox tower below shows us which pairs of chemicals will react spontaneously, giving our cells the “shock” of energy they need. How big of a shock is it? What’s the potential of the battery? The example arrow is a guide. Glucose gives up electrons (oxidation) and the second part (arrow tip) is backwards from the way it’s written — NAD+ receives electrons (reduction).
Now, what is the total potential? Look again at the glucose half of the reaction. Glucose is being oxidized, but the potentials on the diagram are reduction potentials! What do we do? Flip the sign — the potential of the glucose ovidation is +500 mV instead of -500 mV. NAD+ is being reduced, so we can use the potential as written and add the two half-reactions together: 500 mV — 320 mV = 180 mV. The overall potential of the donor/acceptor pair is positive, providing energy to the cell harnessing the reaction.
The dance of glucose and oxygen involves more than a single reaction, but each step involves this basic electrochemistry. The figure of 500 mV for glucose being oxidized to carbon dioxide is really an aggregate number for all the steps it takes to get there. Glycolysis is the first process in this sequence, in which glucose is gradually cleaved into two molecules of pyruvate. Just this process consists of several steps, but has its own oxidation potential: 720 mV, which is quite high. What allows these simplifications is that the battery analogy holds for reactions in series. Just like batteries strung together, we add the potentials of each reaction in the chain to get the total potential.
Our old friends sugar and oxygen are venerated workhorses for catabolism. Oxygen has an incredibly high potential for reduction (820 mV). Similarly, breaking glucose down to strip it of electrons is a favorable reaction, with an overall potential of 500 mV. When combined, the 1320 mV produced by transforming sugar and oxygen to carbon dioxide and water make aerobic respiration the method of choice when the resources are available.
Metabolic Diversity and Geobacter
In the microbial world, the pickings can be slim. Nutrients are often scarce, and not one electron donor or acceptor fits all. Bacteria and Archaea — collectively prokaryotes, the oldest single-cell domains of life — have had a long time to specialize, and they’ve made great use of it. Prokaryotes have taken to ecological niches the same approach that Americans took to avocadoes and coconut oil: anytime, anywhere, even if it doesn’t make sense. Enter the extremophiles: single-celled organisms that can live in salted meat or environments above the boiling point of water, or receive more than 1000 times the lethal human dose of radiation.
Many of these extremophiles and their less extreme — but still quirky — single-celled relatives make do by adapting to electron donor/acceptor pairs that are completely unusable for human cells. Nitrate, sulfate, acetate, lactate, and hydrogen gas are all examples of primary donors and acceptors for some species of prokaryotes. In 1987, Derek Lovely found a new type of bacteria living in the sand of the Potomac River. Geobacter metallireducens (as it was later named) is one of several species in the genus Geobacter, and this group of tenacious microbes often use iron as an electron acceptor. As we breathe oxygen, Geobacter can breathe metal. Bacteria have no lungs, so this is not breathing as we know it. Our electron acceptor is oxygen, but oxygen kills Geobacter.
In Figure 3, oxygen is the “best” electron acceptor. Coming in second is iron. Geobacter evolved such that it lives in anaerobic environments, reducing ferric iron (Fe(III), “missing” three electrons) to ferrous iron (Fe(II)). Since oxygen is a better electron acceptor than iron, it will start reacting with (and disabling) the delicate machinery that Geobacter has evolved. Think back to the circuitry example: if oxygen gets into the environment, it’s like plugging a car battery into a tiny lightbulb. Sure, there’s enough power, but if the circuit is only built to operate on a AAA battery, the bulb’s filament will be vaporized.
How does one breathe something that’s a solid? Some species of Geobacter can attach to iron minerals and to each other and send electrons back and forth via “nanowires” — modified protein tubes that conduct electricity. Some can also use “electron shuttles,” small molecules where an electron can be attached and the molecule ejected from the cell to be delivered to the electron acceptor.
An Adaptive Hero
Iron is not the end of the story. Having adapted special methods for reducing metal solids, Geobacter opened the door to other elements. Derek Lovely (and many others since 1991) have been observing Geobacter species and found that they are not particularly picky. When placed in a soup containing ferric iron and highly charged uranium (U(VI), uranium but missing six electrons), G. sulfurreducens began using its electron-slinging abilities to throw two electrons onto uranium, resulting in U(IV). As it turns out, Geobacter can do this same trick with many different types of rare metals. Cobalt, silver, and mercury can all be the electron acceptor for Geobacter in some situations, and even more metals seem likely.
Unlike iron, Uranium isn’t an important piece of a healthy diet. Uranium occurs naturally — and contrary to its reputation, isn’t typically dangerous because of its radioactivity. The dangerously radioactive fraction is small in natural deposits and must be enriched to be used as fuel. However, like most heavy metals, uranium is treated as a contaminant. Some evidence exists that uranium in the blood may cause damage to the kidneys and accumulate in the bones.
A variety of human activities may be creating concentrations of uranium well above regulated levels in groundwater. Tailings from old uranium mines, declining water tables, and nitrate pollution can all transform uranium bound in minerals into dissolved salts in the groundwater. Aside from better water management practices, cleanup may be required for some sites.
Groundwater treatment is difficult. It is impossible to know exactly how the water flows and where contaminants are and are not. Sampling wells to where an aquifer is contaminated (and where the contamination is going) is an act of statistical and mathematical gymnastics. Treatment methods are diverse, and range from cheap (digging a trench and filling it with iron filings) to expensive (pumping out groundwater, treating it, and injecting it back into the ground for years). A newer strategy called bioremediation relies instead on the ingenuity of microbes to freshen up the soil and water.
Bacteria in the soil and groundwater will cut a deal: if we provide the right electron donor or acceptor, they can use our target contaminant as the other half of the catabolic pair. For example, if you inject an oxygen-rich compound into a soil contaminated with some gasoline, some bacteria will “breathe” the oxygen and “eat” the gasoline. Geobacter shows a similar willingness. Recall that it can reduce U(VI) to U(IV). The former is soluble and readily flows through groundwater, but the latter forms a mineral called uraninite, which is insoluble. If we can feed Geobacter an electron donor like acetate (think vinegar)it will start reducing the uranium, which will then drop out of the water as a solid!
A Word of Fascination
Geobacter is not going to stop climate change or allow us to dispose of nuclear sludge anywhere we please. Its use as a remediation technology is still very exploratory, but also very real. Uranium is not the most pressing groundwater contaminant, either. Many of the most worrisome culprits in aquifers we rely on for drinking and irrigation are anthropogenic: chlorinated solvents, hydrocarbons, and pesticides. Natural contaminants exist, too, such as nitrate and arsenic. Arsenic is much more potent a toxin than uranium, and aquifer mismanagement may be responsible for rising arsenic levels in Bangladesh.
Environmental disasters aside, the purpose of this writing has been to provide an introduction to the concept of metabolic diversity in the minuscule forms of life so critical to the planet’s operations. Through this anecdote, I hoped to share with you the seed of an idea, that single-celled organisms can accomplish feats that go mostly unnoticed but may be beneficial to us. We just need to pay close attention.
Acknowledgements
Thank you to Derek Lovely, Avi Flamholz, and my mom for their contributions as readers of this blog post.
Derek Lovely is a Distinguished University Professor at the University of Massachusetts-Amherst and continues to explore microbial geochemistry. Check out his work at Geobacter Project!
Avi Flamholz is an NSF fellow and graduate student at UC Berkeley. He studies microbial geochemistry as well, and some of his writing, along with a fun interview about the history and mechanics of photosynthesis, can be found here.
Questions or important details I missed? Emotional declarations or poetry inspired by Geobacter? Email me at noahgblogs@gmail.com, tweet to me @tinyscienceblog, or choose not to interact with me at all.
